Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria
نویسندگان
چکیده
BACKGROUND Previously the angiotensin II receptor blocker Irbesartan has been demonstrated to reduce the risk for progression from microalbuminuria to macroalbuminuria in type 2 diabetic patients. The purpose of this study was to evaluate the effect of treatment with Irbesartan in type 2 diabetic patients with microalbuminuria on the urinary proteome. METHODS High-resolution capillary-electrophoresis coupled to mass-spectrometry (CE-MS) was used to profile the low-molecular-weight proteome in urine of a subgroup of patients from a two year randomized irbesartan versus placebo therapy trial, which included hypertensive type 2 diabetic patients with microalbuminuria on ongoing antihypertensive medication (IRMA2-substudy). RESULTS We demonstrate that the therapy with 300 mg Irbesartan daily over a period of two years results in significant changes of the urinary proteome. Both, a classifier developed previously that consists of urinary peptides indicative of chronic kidney disease, as well as several individual peptides changed significantly after treatment. These changes were not observed in the placebo-treated individuals. Most prominent are changes of urinary collagen fragments associated with progression of diabetic nephropathy, indicating normalization in urinary peptides. CONCLUSION CE-MS analysis of urine enabled identification of peptides as potential surrogate markers for renoprotection in microalbuminuric type 2 diabetic patients, which show persistent improvement after longterm treatment with Irbesartan. The results suggest that a major benefit of treatment by Irbesartan may be improvement of collagen turnover, reduction of fibrosis. They further suggest that urinary proteome analysis could be utilized to assess potential benefit of therapeutic intervention, providing statistically significant results even on a small population.
منابع مشابه
Comparison of the Antialbuminuric Effects of L-/N-type and L-type Calcium Channel Blockers in Hypertensive Patients with Diabetes and Microalbuminuria: The Study of Assessment for Kidney Function by Urinary Microalbumin in Randomized (SAKURA) Trial
OBJECTIVE To clarify whether the L-/N-type calcium channel blocker (CCB) cilnidipine is more renoprotective than the L-type CCB amlodipine in patients with early-stage diabetic nephropathy. METHODS In this prospective, multicenter, open-labeled, randomized trial, the antialbuminuric effects of cilnidipine and amlodipine were examined in renin-angiotensin system (RAS) inhibitor-treated patient...
متن کاملKidney function during and after withdrawal of long-term irbesartan treatment in patients with type 2 diabetes and microalbuminuria.
OBJECTIVE Irbesartan is renoprotective in patients with type 2 diabetes and microalbuminuria. Whether the observed reduction in microalbuminuria is reversible (hemodynamic) or persistent (glomerular structural/biochemical normalization) after prolonged antihypertensive treatment is unknown. Therefore, the present substudy of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria S...
متن کاملمیزان بروز میکروآلبومینوری و عوامل خطر همراه در بیماران دیابتی نوع 2
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متن کاملبررسی میکرو آلبومینوری و عوامل خطر مرتبط با آن در بیماران دیابتی نوع دو
Background and purpose: Diabetes mellitus due to impaired insulin secretion, leads to short term and long term complications. Some of these complications are diabetic nephropathy and renal failure. The prevalence of diabetic nephropathy is 20-30% in Iran and 20% of type II diabetes and 75% of type I diabetes are affected in 20 years. Microalbuminuria has utmost importance as a marker of renal d...
متن کاملفراوانی نسبی میکروآلبومینوری در بیماران دیابتی نوع 2 مراجعه کننده به درمانگاه دیابت مجتمع بیمارستانی امام خمینی در سال 81-1380
Introduction: The urinary excretion of minimal quantities of albumin (microalbuminuria) is predictive of renal failure and cardiovascular mortality. The detection and prompt treatment of microalbuminuria is crucial to the prevention and progress of renal failure in patients with diabetes. The aim of this study is to evaluate the relative frequency of microalbuminuria in different age groups o...
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